Dry eye disease is an affliction that impacts as many as 20 percent of the U.S. population over age 50 and may be even more prevalent around the world. Dry eye disease can impact women more than men, and can have a dramatic and negative impact on quality of life and economic productivity. The etiology of dry eye is complex, involving the autoimmune system, and both the exocrine and endocrine systems. Currently, treatment is primary palliative, involving warm compresses and eye drops. RESTASIS provided by Allergan, Inc. seeks to reduce inflammation to promote tear flow. TearScience recently released LipiFlow to attempt to thermally improve meibomian gland function.
Corneal dystrophies include disease and injury of the epithelium, stroma and endothelium. 2.5 million Americans suffer from eye injury each year. There are at least 80,000 corneal transplants and grafts annually. Keratoconus affects 1 in 2000. 35 million Americans wear contact lenses and approximately 3 million Americans undergo some sort of refractive surgery each year. The contact lens industry is 3 billion dollar retail industry, and investment in surgical procedures and devices for management of eye disease and for refractive correction continues to be strong.
Dry eye disease is diagnosed primarily using a patient questionnaire, with support of slit lamp, transdermal illumination, staining, and tear film interferometry. Placido disk cornea topography remains the primary instrument for assessing cornea shape. Each of these visualization techniques is limited in their ability to assess functional causes of dry eye or fine ultrastructure associated with dry eye, tear film, or cornea abnormalities. Additional diagnostic and research techniques are warranted.
The high resolution of spectral domain optical coherence tomography (SDOCT) is beginning to generate interest in cornea imaging. However, like all SDOCT systems that image the anterior with telecentric optics, the signal typically falls off away from cornea center, constraining the field of view. Additionally, away from cornea center the scanning optical coherence tomography beam impinges the cornea at an increasingly oblique angle. The beam then refracts into the cornea. The image on the screen follows the scanning ray; a correct view of the cornea requires a well-understood “dewarping” step.
The issues with respect to SDCOT discussed above are illustrated in, for example, FIGS. 1A-1C. These figures present a selection of inner eye lid images obtained using Spectral Domain Ophthalmic Imaging System provided by Bioptigen, Envisu™ R2300 Spectral Domain Ophthalmic Imaging System. The images in FIGS. 1A-1C illuminate the capabilities of SDOCT in imaging inner eye lid fine structure. In particular, FIG. 1A illustrates a series of B-scan on the left, which follow the path of a Meibomian duct (circled) from the surface of the marginal conductiva to the deeper layers. The image on the right in FIG. 1A is a volume intensity projection through the entire stack of B-scans in a 5 mm×5 mm volumetric image if the marginal conjunctiva area. Referring now to FIG. 1B, the electron micrographs on the right illustrate the distribution of Meibomian glands around the ducts in the tarsal and marginal portion of the conjunctiva. The B-scans on the left appear to illustrate the ducts and surrounding glands in the tarsal conjunctiva of a normal volunteer. The B-Scan on the top also shows what appears to be a global cell. Finally, FIG. 1C illustrates an anatomical drawing of an eyelid showing Meibomian glad on the left. On the right, FIG. 1C illustrates a cross-section of the eyelid to sclera illustrating tear film and two goblets.
Current clinical retina SDOCT systems are increasingly retrofitted for cornea imaging, but as they have a limited imaging depth appropriate for retina, the depth of view for the cornea is wholly inadequate for limbus-limbus imaging of the cornea. Bioptigen (Envisu™ R4300) has developed a deep imaging SDOCT system. As illustrated in FIG. 2, the Bioptigen system has a 7.5 mm depth of view and may be suitable for direct full range imaging of anterior chamber. Thus, this system provides full range anterior segment SDOCT with 7.5 mm depth of view, a 4.0 μm resolution acquired at 20 frames per second.
As further illustrated in FIGS. 3A-I, the Bioptigen system is capable of full depth imaging, but does not solve problem of “warping” due to refraction at the cornea surface. FIGS. 3A-through 3I illustrate a corneoscleral junction with contact lens; keratoconus; riboflavin over partially epithelium stripped cornea after cross-linking; corneal opacity; opacity post treatment with PTK; FS LASIK flap; Microtome LASIK flap; DSAEK with trapped bubble; DSAEK bubble eliminated, respectively. The subject in the image of FIGS. 3A through 3I is wearing a contact lens; the difficulty of oblique imaging is apparent when one tries to resolve the contact lens fit at the limbus. Another problem is that visualization of the angle is hampered, as the scanned ray travels a greater distance through the sclera to reach the angle than would be necessary on normally directed viewing. Accordingly, improved systems are desired.